SPID#: 1 The aim of this project is to characterize the effects of cocaine and related stimulants on the central nervous system and behavior in nonhuman primates. Drug effects on learned, conditioned operant behavior is a major focus. Methods used include changes in schedule-controlled behavior as an index of central nervous system activity, the intravenous self-administration of drugs as indicative of reinforcing efficacy or abuse liability, and drugs as discriminative stimuli controlling behavior. Through the use of monoamine agonists and antagonists, this laboratory has demonstrated the involvement of specific neurotransmitter systems in the behavioral, reinforcing and discriminative effects of cocaine and other selected drugs associated with high abuse liability. Progress during the previous calendar year further clarified the role of the serotonergic system in the mediation of cocaine's effects on behavior. In addition, in vivo microdialysis techniques were developed for use in conscious monkeys to allow for the measurement of direct neurochemical changes associated with drug effects on behavior. Pronounced increases in extracellular dopamine were demonstrated during cocaine administration. Subsequent experiments will investigate the ability of serotonergic compounds to block cocaine-induced neurochemical changes. The long-range objective is to characterize the behavioral and neurochemical effects of cocaine and to identify other drugs that may have therapeutic value in treating stimulant abuse.